Velvet Antler

The Science, Historical Medical Uses
And Performance Enhancing Effects

EA2000 Elk Antler supplement

Dr. John Church, Game Farm Manager for Canadian Rocky Mountain Resorts, is responsible for the construction of game farm facilities and the purchase, care and management of wapiti, bison, white deer and reindeer. Dr. Church received both his B.Sc. in Wildlife Management and his Ph.D. in Rangeland and Wildlife Resources from the University of Alberta. In between these studies, he received his M.Sc. in Biology: Applied Animal Behavior at Dathousie University in Halifax. In addition to his current position, Dr. Church has worked as a researcher at the Centre for Agricultural Diversification at Dawson Creek, BC working with bison, and as an instructor in the Diversified Livestock program at Lakeland College in Vermilion.

1. Historical Use of Velvet Antler

The importance in traditional Chinese medicine of the advancement of health and the prevention of ill health is in direct disagreement with western medical practice, which is more impressed with the treatment of ill health (Fulder 1980a). In fact the entire culture of traditional Eastern medicine is one of the quest for health rather than the treatment of ill health (Brekhman 1980; Kaptchuk and Creacher (1987)). Historical Literature in both Chinese and Korean describes antler as soft growing tissue with velvet, and highly regarded the efficacy of antler as preventative medicine. Currently, there is an expanding stake in medicinal products which are alternative in nature and have tonic effects or effects on well-being. Holistic medicine is one area where velvet antler has traditionally found a niche in oriental medicine. It has also been used historically in the specific treatment of a number of conditions including anemia, arthritis, impotence, mynoxenia, dysfunctional uterine bleeding, dizziness and vertigo, insomnia, amnesia, wounds and pain (Kong and Ko 1987; Yoon 1989).

The use of velvet antler as a medicine and the momentousness of sexual well-being in Chinese tradition, have consummated in velvet antler being regarded by western commentators as an aphrodisiac. This characterization is unfortunate since in western countries, it has resulted in velvet antler being ignored as a serious candidate for pharmacological activity or application. In this regard, it is fairly ironic that a Korean doctor ('loon 1989) observes that about 10% of velvet antler users are children, In Korea, antler is regarded as a fundamental component in herbal medicine, used for its preventative and restorative functions.

It is theorized that deer antler amplifies the body's metabolism in general, preserves and renews injured organs and tissues (accelerating healing and recovery from injury), assists immune and phagocytic functions (anti-inflammation, anti-arthritis, anti-stress), moderates the aging process, has hypotensive-vascular effects, and ameliorates both gonadotrophic and thyroid function. This report will attempt to address the scientific validity of these traditionally held beliefs.

2. What is Velvet Antler?

The name "antler" comes from the Latin word "anteoculae" meaning "in front of the eyes". Antlers are appendages of the skull, created from a thick bony core and upheld on permanent skin covered pedicles (protuberance of the frontal bone). The creation of antlers by mates is observed after pedicle development from the periosteum of the frontal bones of almost all members of the deer family Cervidae (Goss 1983).

Unlike horns in cattle, antlers are cast off every year. Deer or cervids such as caribou, wapiti and moose grow antlers while cattle or bovids including mountain goats, bighorn sheep, bison and pronghorn antelope possess horns. With the exception of reindeer and caribou (Rangifer tarandus), only the males grow antlers.

3. Velvet Antler Composition

The developing antler is composed of an aggregate of distinct cell types including fibroblasts, chondroblasts, chondrocytes, and osteocytes (Banks and Newberry 1982). Growing antler tips are composed of minute millimeters of undifferentiated mesenchymal cells that begin to differentiate very abruptly as cartilaginous tissue. Afterward the cartilage is replaced by bone, under the influence of testosterone and its metabolites, and the velvet is shed leaving mature hard antler (Fenessy and Suttie 1985), Consequently when velvet antler is harvested at suitable stages for use as high quality oriental medicines, it is actively growing cartilage-type tissue which is not of uniform composition, that is sought. Chemical identification of antler is currently being explored by Canadian scientists to identify the active components, and to locate the quality and criterion of antler and antler byproducts by utilizing chemical markers (Sunwoo et at. 1995).

The rate of mineralization or calcification of velvet antler is commonly referred to as a gauge of the probable pharmacological quality, with heavily calcified velvet antler being downgraded. The constituents of dry matter analysis of velvet antler demonstrate that collagen, calcium, phosphorus, and magnesium increase upward, while protein and lipids decrease downward from the tip to the base of the main beam in growing antler.

However this largely depends on the stage of growth as is indicated by the relative mineral content in the lower section of velvet antlers cut at different stages of growth after casting. The effect of stage of development on lipid content is also significant. Amino acid contents stated as a percentage of total protein and lipid is considerably higher in the tip section, from which the antler grows. The concentrations of uronic acid, sulfated glycocaminoglycan, and sialic acid decrease from the tip portion downward towards the base of the growing antler. The tip segment has the best proportions of tyrosine and isoleucine and the smallest proportions of glycine and alanine. Linolenic acid was discovered in the tip segment only.

Recent studies at the University of Alberta, Canada has shown that velvet antlers contain chondroitin sulfate as a major glycosaminoglycan with small amounts of keratin sulfate, hyaluronic acid, and dermatan sulfate (Sunwoo et al. 1997). Even more recently, the same researchers in Canada have extracted and characterized proteoglycans from the cartilaginous portion of velvet antler from wapiti, and found two types of proteoglycans including large chodroitin sulfate proteoglycan and small proteoglycan, decorin (Sunwoo 1998).

Research back in 1988 established that chondroitin sulfate A is an extremely potent anti- inflammatory agent. There are convincing opinions that there is substantial difference in mineralization between species of deer at the same stage of growth, but this has not been quantified. The compositional changes from the tip to the base are reflected in both Chinese (Wang and Zhou 1991) and Korean (Yoon 1989) medical systems which broadly classify the various parts of velvet antler. The tip is referred to as the wax piece, the next section is the blood piece, and finally the bottom is known as the base or bone piece (Fennessy 1992). Once the velvet antler is harvested, blood quickly seeps away from the tip region, although inverting the antler will help alleviate this problem. Depending on the drying methods, the dried product can have considerable blood in this section. However the traditional Chinese drying methods result in the tip remaining empty of blood; therefore its often categorized as the wax piece.

Dr. Peter Fennesy, general manager of the Invermay Research Centre in Otago, New Zealand has stated that initial research data indicates that elevated levels of a natural growth hormone called insuline-like growth factor (IGF-1) exists in the blood of deer during the antler growth cycle a well as receptors to IGF-1. As human beings age, growth hormone levels decline along with IGF-1, which results in muscular atrophy. Velvet antler is most likely an unrefined source of IGF-1 that can improve muscular development. Cell culture studies have discovered that the administration of IGF-1 and 2 can have a significant effect on the cells in velvet antler. These growth factors augment cell division in undifferentiated cells in the fibroblast zone, the growing tip and the cartilage zone. These finding indicate that IGF-1 and 2 are likely important facilitators for antler growth. The significance of these factors to the cell regeneration processes in humans has recently been a source of much speculation.

Subsequent studies at Oxford University in England has resulted in the discovery that IGF-1 increases the release of alkaine phosphatase and cell growth in the distal antler tips of male red deer (Cervus elaphus). This growth factor increases the rate of cell division in the inner layer of the perichondrium, the reserve mesenchyme and the cartilage zone. The biochemistry that contributes to the rapid growth of velvet antlers probably has undiscovered medical potential for humans with regards to increasing cell growth and repair.

4. Traditional Medicinal Uses of Antler

In Oriental medicine, the different sections of velvet antler have assorted uses. The upper two sections are often used as preventative tonics in children while the middle portion is often used to treat arthritis and osteomyelitis. The lowest part of velvet antler is often administered to older people to help prevent calcium. Velvet antler has also been used in childbirth to assist delivery, anemia, menopausal disorders, impotence and spermatorrhea.

As a medical product, velvet antler is dried, processed and used in a variety of treatments. Traditional methods of processing antler were designed to avoid spoilage during the slow drying process.

Processing generally involves repeated immersions in boiling water followed by drying using either heat or open air drying. Although no details are given, studies cited by Russian scientists Vudin and Oubryakov (1974) state that boiling of the antlers, one of the traditional steps commonly used is contraindicated in terms of its effects on pharmacological activity. There are many different forms in which dried antler is processed into for use, including slices, powders and extracts. Velvet antler in Asia is often included as a single component of prescription medicine while other over-the-counter preparations that also include velvet antler are combined with other traditional medicines, especially herbs.

5. Performance Enhancing Effects of Velvet Antler

Velvet antler has often been regarded as having performance enhancing effects on the human body. There is scientific evidence from a number of studies that have revealed such effects in both animals and humans. For example, Brekhman et al. (1969) showed that pantocrin increased the working capacity of mice. Russian scientists Yudin and Dubryakov (1974) have reported that control athletes on an exercise cycle performed 15 kg/m of dynamic work whereas those given pantocrin increased this considerably to 74 kg/rn and those given rantarin (a preparation of reindeer antler) increased to 103 kg/m. In a like manner, the athletic performance in a 3000m run was enhanced following patocrin administration (Brekhman et a 1969). According to Russian scientist Korobkov (1974, cited by Fulder 1980b) with regards to the use of velvet antler in athletes, the action is primarily aimed at accelerating the restorative processes after intensive activity and at increasing the body's resistance to unfavorable external influences. In essence, pantocrin and other naturally occurring substances in velvet antler have served to accelerate the body's natural restorative processes.

For well over a decade, Dr. Arkady Koltun, MD, Ph.D., Chairman of the Medical Committee for the Russian BodyBuilding Federation, has conducted research into anabolic agents that are known to improve performance, strength, and musculature in athletes. In studies with Russian kayakers, weightlifters, bodybuilders and powerlifters, Dr. Kottun found that velvet antler has both myotropic (increases muscular strength) and neurotropic (nerve strengthening) properties. He also found properties in antler that are beneficial in treating infectious disease, fatigue and hypertension.

The performance enhancing effects of velvet antler are likely the results of increasing the circulating levels of androgens in the blood of these athletes. There is now considerable evidence for the gonadotrophic effects of velvet antler. Androgens (testosterone and its metabolites) are known to stimulate the development of seminal vesicles and the prostate gland of sexually immature neonate rats, or retard the degeneration of these organs in newly castrated animals. Velvet antler preparations pantocrine and rantarin have all been shown to have androgenic effects.

Haematopoietic effects of velvet antler have been demonstrated in numerous experiments. Preparations of velvet antler have been shown to stimulate red blood cell synthesis and increase erythropoietic activity in cases of drug induced anemia in rabbits and rats. It seems likely that such erythropoietic activity may well be responsible for at least part of the stamina-improving effects of velvet antler preparations in distance runners. In this sense, the responses would be similar to those ascribed to blood-doping where an athlete in re-transfused with his own blood prior to competition.

6. Pharmacological Effects of Velvet Antler

The documented effects of velvet antler in studies with laboratory animals are numerous, generated mainly from the former Soviet Union, as well as Korea, China, Japan, Hong Kong, New Zealand and recently Canada. Much of the Russian work is concerned with the extracts of pantocrin or rantarin.

The reported pharmacological effects and evidence for bioactivity include the following:

• stimulating and tonic effects
• androgenic / gonadotrophic effects
• haemotopoietic effects
• hypotensive and cardiovascular effects
• anti-stress effects
• growth-stimulating effects
• retardation of aging
• accelerated recovery from injury
• anti-tumor effects
• anti-cholesterol effects

The biological activity is highly correlated with several of the extract components including pentose sugars, free amino acids, free fatty acids and phospholipids. The Russian extract pantocrin has demonstrated hypotensive effect in animals under anesthesia. The effect is transient, causing a drop in arterial pressure of up to 50%- The hypotesive effects of the alcohol extract pantocrine are likely due to the presence of lysophophtidyl cholines.

Some further evidence of potent pharmacological activity of velvet antler or antler preparations include evidence that treatment with velvet antler can protect against shock or stress. For example, Kang (1970) reported that antler pre-treatment has reduced cell degradation in rats subjected to heat stress, cold stress or electric shock. Vudin and Dubryakov (1974) reported that rantarine alleviated the adverse effects of stress in normal stress-related responses such as hypertrophy of the adrenals, involution of the thymus gland and reductions in the weight of the liver and kidneys when laboratory animals were administered the extract.

Wang et al. 1988 claims that it is the polysaccharide content that is responsible for the anti-ulcer effects of velvet antler preparations. Kim and Lirn (1977) cited Russian studies showing that treatment of patients with rantarin prior to surgery for gastrointestinal tumors resulted in reduced stress responses in rantarin-treated patients. Velvet antler treated rats have also been shown to better tolerate carbon tetrachloride-induced liver damage with some evidence of different responses with velvet of different sources, presumably due to the preparations being from velvet harvested at different stages of growth. Beubenick (1986) mentioned that an extract from the growing antler tip section facilitates healing of epidermal wounds in rats. Thus from a variety of sources, there would appear to be good evidence for the efficacy of velvet antler preparations in the treatment and alleviation of stress related conditions.

In Korea, a study was conducted to evaluate the nutritive value of velvet antler on blood cholesterol levels in rats. The blood cholesterol level was significantly reduced in the rat when the diet was supplemented with velvet antler. In addition, body weight gain, feed intake and feed efficiency remained unchanged, proving lowered cholesterol levels were not due to these factors. Korean researchers have determined that feeding velvet antler to broiler chickens resulted in a small but significant increase in growth rate and food conversion efficiency over an 8 week period. Interestingly, the weight of the testes was significantly increased while the thyroid weight was decreased.

Studies in Japan (Wang et a 1988) have shown marked effects of velvet antler preparations on biochemical parameters related to aging in senescence-accelerated mice (SAM), a model for senility. The hot water extract of velvet antler was administered for 8 days. Treated mice showed significant improvements in parameters normally associated with senility, including an increase in plasma testosterone. The effects were generally observed only in the SAM strain and not in the control strain of mice, suggesting that velvet preparation may exert an anti-aging effect in senile animals.

Wang et al. (1988) demonstrated that mice subjected to chloroform damage to the liver that is caused by an increase in free radicals could be alleviated by treatment with velvet antler. Further studies (Wang et at. 1988) revealed a direct effect on the rate of protein synthesis in the liver and kidney apparently mediated by an increase in RNA polymerase activity (RNA polymerase regulates RNA transcription from nuclear DNA). The studies carried out by Wang and his associates (1988 a,b,c) appear to be careful, well thought out and very credible. These studies provide a good starting point for further work in this area. Effects such as those reported by Wang et at. (1988b) in the kidney (and in the liver) are also produced by androgens, again suggesting that some more intensive research directed towards the steroid-like activities of velvet antler preparations would be beneficial.

Prostaglandins discovered in velvet antler have been recognized as anti-inflammatory components that reduce the body's reaction to injury, swelling, infection, pain and arthritis. Also, the collagen in velvet has been demonstrated as a healing agent when ingested and when applied as a topical skin treatment. Studies conducted in China on an extract of antler have shown anti-inflammatory properties by reducing acute and chronic inflammation in rats. The extract reduced ascorbic acid and cholesterol contents in the adrenal glands and decreased the serum hydrocortisone level in rats. The results of these studies indicate that the antler contains anti-inflammatory and other agents that are beneficial for reducing the body's response to arthritis and injury and cardiovascular health.

In biochemical studies conducted at the Oriental Medicine Research Center of the Kitasato Institute in Tokyo, Japan, polysaccharides have been identified in velvet antler that tend to reduce the blood's tendency to clot and to thin the blood. This effect indicates that antler would contribute to improved circulation, decreased risk of stroke and improved general cardiovascular health.

Japanese researchers have also investigated the effects of pantocrine on the recovery of rats and rabbits from an induced whiplash-type injury. Pantocrine treatment enhanced glycolysis in nervous tissue, an effect actually specific to neural tissue (Takikawa et at. 1972 a,b). There is also support for such effects from double-blind study in humans suffering from cervical injuries, where pantocrine treatment aided recovery (Uelki et al. 1973).

Li and Wang (1990) cited Chinese studies showing that treatment of rats with a velvet antler extract resulted in marked increases in the numbers of monocytes, suggesting the presence of components that might affect the immune system. In New Zealand, researchers have found that extracts from velvet antler have reduced tumor cell growth (Suttie et al. 1994) and may in the future be utilized in the fight against cancer. Anti-tumor activity of antler and antler fermented in Bacillus P-92 were demonstrated in mice. Fermentation increases the amount of free amino acids, polypeptides and other compounds that produce healthful effects. The survival rate of mice with tumors increased from 25 to 40 percent. The neutrophil levels in the mice were increased 2 to 3 fold for antler and 3 to 4 fold for fermented antler. The higher levels of neutrophils increased the body's ability to resist injury and disease. Results suggest that fermentation increases some of the health benefits of velvet antler.

Recently, Canadian researchers at the University of Alberta, have demonstrated that the glycosaminoglycans in the water soluble fractions of velvet antlers have growth promoting effects on cells (Sunwoo and Sim 1996). The researchers at the University of Alberta observed a number of interim results from the consumption of velvet antler extracts in addition to enhanced cell and whole animal growth including; anti-stress and anti-inflammatory properties, increases in HOL (desirable) cholesterol and increases in red blood cell counts (Sim et at. 1995a, Sim et at. 1995b, Sunwoo, 1988, Sunwoo et al. 1995, Sunwoo et al. 1997, Sunwoo and Sim 1996).

7. Scientific Explanation for Velvet Antler

Clearly the case for the pharmacological or bioactivity of velvet antler is very strong. However, there is not yet a unifying hypothesis to explain the many and varied effects of velvet antler in different animal species. The hypotensive effects have been explained as at least partly due to the actions of choline compounds. Choline compounds are not unique to velvet antlers. Other facets of biological activity ascribed to velvet antler are not so easy to explain, although Wang et al. (1985 cited by Wang et al. 1988) states that the anti-ulcer effects of velvet antler preparations is due to the presence of various polysaccharides. Velvet antler likely contains peptide growth factors (e.g. epidermal growth factor EGF), but concentrations would be low and would the concentrations retain their biological activity through processing? In respect to growth factors, however, EGF has been shown to replace estrogen in the stimulation of female genital tract development, a phenomenon that raises fascinating questions about the interrelationships between steroids and peptide growth factors. Steroids and growth factors may survive processing but to date there has been no systematic evaluations of the steroid composition of velvet antler published in the scientific literature. However, it seems most unlikely that steroids present in the velvet antler would be solely responsible for the observed androgenic effects. Rather compounds present in the antler are inducing steroid synthesis in the treated animals, presumably via effects on the hypothalamus or pituitary gland and then on the adrenal or testis.

Fulder (1980) proposed a general theory to explain the effects of these "antifatigue substances' which include pantocrin, in that the biologically active components are generally glycosides, where the active chemical groups are linked to sugar molecules. Fulder proposes that the primary site of action of the glycosides is the hypothalamus and the pituitary gland. The most commonly used glycoside in western medicine is digitoxin, originally isolated from the plant commonly referred to as foxglove, which is well known and has medically accepted and potent effects of the cardiac system. This area of the glucoside/glycoside link is potentially very important and one where future studies might provide more insight into the nature and efficacy of some of the compounds present in many of the traditional medicines of the East.

8. Future Directions for Velvet Antler Research

A more scientific understanding of the bioactive components of velvet antler is necessary to define that nature of the compounds and their effects in animal systems. This is necessary to define the effects of drying and processing methods on bioactivity and to maintain and improve product quality. It is also necessary in the search for new bioactive compounds which may be unique to velvet antler and which could provide new insights into the control of differentiation, growth and metabolism. One of the prime objectives must be to develop in vitro systems to assay the bioactivity of velvet antler preparations. This may be difficult in the sense that some of the reported effects of velvet antler would appear to be dependent on an integrated whole animal system. There is also the possibility that some of the effects are due to the synergistic effects of two or more components present in the velvet antler. The whole area, though clearly one of considerable complexity, is likely to be very rewarding.

9. Scientific References of Velvet Antler

Adams, J. L. 1979, Innervation and blood supply of the antler pedicle of the Red deer. N L Yet J. 27: 200-201.

Bae, D. 5. 1977. Study on the effect of antler on growth of animals, Ill. Effect of antler on the ability of spermatogenesis of cocks fertilization. Korean J Anim Sd 19: 407-412.

Banks, W. J. and J. W. Newberry. 1981 Light microscope studies of the ossification proccess in developing antlers, In Antler Development in Cervidae. ed. R. D. Boone. Caesar Kleberg Wildlife Research Institute. Kingsville Texas. pp 231-260.

Bubenik, G. A., Bubenik, A.B. 19S6. Phylogeny and ontogeny of antlers and neuro-endocrine regulation of the antler cycle - a review. Saeugetierk. Mitt. 33(2/3): 97-123.

Bubenik GA, Schams 0, White R Rowell J, Blake J, Bartos L Comp Biochem Physiol B Biochem Mol Biol 1997 Feb;116(2):269-277 Seasonal levels of reproductive hormones and their relationship to the antler cycle of male and female reindeer (Rangifer tarandus). Department of Zoology, University of Guelph, Ontario, Canada.

Seasonal levels of LH, FSH, testosterone (T), estradiol, progesterone (P), and protactin (PRL) were determined in the plasma of five adult bulls, and five barren and four pregnant cows of Alaskan reindeer (Rangifer tarandus), which were sampled every 3 weeks for 54 weeks. The male reproductive axis was sequentially activated; LI- peaked in May (2 ng/ml), FSH in June (51 ng/ml), and Tin September (11.8 ng/mt). LH levels in females reached a maximum in both groups at the end of August (the beginning of the rut). Seasonal variation in FSH was minimal in pregnant cows, but exhibited one elevation (41 ng/nl) in barren ones in November. 1 levels in cows remained at barely detectable levels. The decrease of I values observed in both groups in December and March was not significant. PRL peaked in May in cows (135 ng/ml pregnant, 140 ng/ml non-pregnant) and in June in bulls (92 ng/ml). Estradiol was highest in bulls in the rut (August), in non-pregnant cows in January and in pregnant cows in April, shortly before parturition. P levels in the pregnant cows rose from September and peaked (9 ng/mL) shortly before parturition in April. In the non-pregnant females P values increased and decreased several times before peaking (5 ngfml) in March. In the males, the variation of T and estradiol levels correlated relatively well with the antler cycle but in the females the variation of neither estradiol, progesterone nor T appeared to be related to mineralization or casting of antlers.

Breckhman, J. T, V. L Dubryakov and A. L. Taneyeva. 1969. The biological activity of the antlers of deer and other deer species. Izvestii Sibirskogo Otdelemia Akademii Nauk SSSR. Biological Series No. 10 (2):112-115

Breckhman J. T. 1980. Man and biologically active substances: The effects of drugs, diet and pollution on health. Translated by J. H. Appleby. Pargamon Press, Oxford.

Chen X, Jia Y, Wang B Chung Kuo Chung ' Tsa Chih 1992 Feb;17(2):107-110 Inhibitory effects of the extract of pilose antler on monoamine oxidase in aged mice. [ in Chinese) Academy of Traditional Chinese Medicine and Materia Medica, Jilin Province, Changchun.

It was demonstrated that the water extract of Pilose Antler (WEPA) showed a higher inhibitory effect on MAO-B activities in the liver and brain tissues of aged mice, but nearly no effect on NAO A. WEPA could significantly increase the contents of 5-NT, NE and DA in the brain tissues of aged mice. In vitro experiments revealed that the inhibition of WEPA on MAO-B was competitive, but on MAO-A was of mixed-type.

Elliott JL, Oldham JM, Ambler GR, Bass Ji, Spencer GS, Hodgkinson SC, Breier BH, Gluckman PD, Suttie JM Endocrinology 1992 May;1 30(5)2513-2520 Presence of insulin-like growth factor-I receptors and absence of growth hormone receptors in the antler tip, Ruakura Agricultural Centre, Ministry of Agriculture and Fisheries, Hamilton, New Zealand.

Red deer antler tips in the growing phase were removed 60 days after the recommencement of growth for autoradiographical studies and RRAs. Sections were incubated with radiolabeled GM or insulin-like growth factor-I (IGF-I), with or without excess competing unlabeled hormones, and were analyzed autoradiographically. There was negligible binding of [125I]GH in any histological zone of antler sections. [125I]IGF-1 showed highest specific binding in the chondroblast zone to a receptor demonstrating binding characteristics of the type I IGF receptor. The lowest specific binding of [125I]IGF-1 was to prechondroblasts. RRAs on antler microsomal membrane preparations RRAs on antler microsomal membrane preparations confirmed the absence of GH receptors and the presence of type 1 IGF receptors found by autoradiography. These findings suggest that IGF-I may act in an endocrine manner in antler growth through a receptor resembling the type I IGF receptor. The presence of type I receptors in the chondrobtast zone implicates GE-I involvement in cartilage formation through matrixogenesis. There is no support for IGF-I having a major role in mitosis in the antler.

Elliott JL, Oldham JM, Ambler GR, Molan PC, Spencer GS, Hodgkinson SC, Breier BH, Gluckman PD, Suttie JM, Bass JJ . Endocrinol 1993 Aug;138(2):233-242 Receptors for insulin-like growth factor-Il in the growing tip of the deer antler. Department of Biological Sciences, University of Waikato, Hamilton, New Zealand.

Insulin-like growth factor-Il (IGF-II) binding in the growing tip of the deer antler was examined using autoradiographical studies, radioreceptor assays and affinity cross-linking studies. Antler tips from red deer stags were removed 60 days after the commencement of growth, and cryogenically cut into sections. Sections were incubated with radiolabelled IGF-ll, with or without an excess of competing unlabelled IGF-II and analysed autoradiographically. Radiolabelted IGF-II showed high specific binding in the reserve mesenchyme and perichondrium zones, which are tissues undergoing rapid differentiation and cell division in the antler. Binding to all other structural zones was low and significantly (P < 0.001) Less than binding to the reserve mesenchyme/perichondrium zones. Radioreceptor assays on antler microsomal membrane preparations revealed that the OF-Il binding was to a relatively homogeneous receptor population (Kd = 1.3 x 10(-1O) molf with characteristics that were not entirety consistent with those normally attributed to the type 2 IGF receptor. Tracer binding was partly displaceable by IGF-l and insulin at concentrations above 10 nmol/l. However, affinity cross-linking studies revealed a single band migrating at 220 kDa under non-reducing conditions, indicative of the type 2 IGF receptor. These results indicate that, in antler tip tissues, IGF-II binds to sites which have different binding patterns and properties from receptors binding IGF-I. This may have functional significance as it appears that, whilst IGF-I has a role in matrix development of cartilage, IGF-II may have a role in the most rapidly differentiating and proliferating tissues of the antler.

Fennessy, P. F. and J. M. Suttie. 1985. Antler growth: Nutritional and endocrine factors. In: Biology of Deer Production. Wellington, Royal Soc. NZ.

Fennessy, P F 1991 Velvet antler: the product and pharmacology. Proc. Deer Course for Veterinarians (Deer Branch of the NZ Vet Assoc). 8 169-180

Feng JQ Chen D, Esparza J, Harris MA, Muridy GR, Harris SE Biochim Biophys Acta 1995 Aug 22;1263(2):163-168 Deer antler tissue contains two types of bone morphogenetic protein 4 mRNA transcripts. University of Texas Health Science Center at San Antonio 78284-7877, USA.

Previously we isolated a bone morphogenetic protein 4 (BMP-4) cDNA from human prostate cancer cells and found that the 5' noncoding exon 1 of this BMP-4 cDNA was different from that of human bone cell BMP-4 cDNA. Recently we identified two alternate exon 1s, IA and 18, f or BMP-4 gene by reverse transcription-polymerase chain reaction (RT-PCR) assays from fetal rat calvarial osteoblasts. In order to further examine alternate exon 1 usage in the BMP-4 gene, we screened deer antler tissue cDNA library. We isolated two types of cDNA clones encoding BMP-4 from this deer antler cDNA library. Sequencing of these clones have revealed a single open reading frame encoding a 408 amino acid protein. Comparison of 5' noncoding exon I portion of these cOMA sequences with those of human bone and prostate BMP-4 cDNA sequences and mouse BMP-4 genomic DNA sequence demonstrated that deer antler tissue expresses both exon 1A and 18 containing BMP-4 mRNA transcripts. This suggests that BMP-4 gene may contain alternate promoters or alternate splicing sites in deer antler tissue.

Feng JQ Chen D, Ghosh-Choudhury N, Esparza J, Mundy OR, Harris SE Biochim Biophys Acta 1997 Jan 3;1 350(1):47-52 Bone morphogenetic protein 2 transcripts in rapidly developing deer antler tissue contain an extended 5 non-coding region arising from a distal promoter. Department of Medicine, University of Texas Health Science Center at San Antonio 78284, USA.

To understand the regulation of the BMP-2 gene expression, we recently isolated the BMP-2 gene from a mouse genomic library and characterized the exon-intron structure and promoter. RNase protection assay using poly (A)- RNA of mouse osteoblasts demonstrates that two regions in BMP-2 gene are protected by antisense mouse BMP-2 RNA probes. These results demonstrate that BMP-2 gene utilizes two alternative promoters, a distal and a proximal promoter. in the present study we demonstrate that BMP-2 mRNA from rapidly growing deer antler tissue has an extended 5' non- coding region compared with the human and rat BMP-2 mRNA. The extended 5' non-coding region in the deer mRNA represents transcripts from the upstream distal promoter. This is the first evidence of a natural BMP-2 mRNA from a bone-forming tissue that most likely initiated from the distal transcription start site.

Fulder, S. 1980a. The hammer and the pesstle. New Scientist. 87 (1209): 120-123

Fulder, S. 1980b. The drug that builds Russians. New Scientist 87 (1215): 516-519.

Garcia RL, Sadighi M, Francis SM, Suttie JM, fleming JS J McI Endocrinol 1997 Oct; l9(2):173 Expression of neurotrophin-3 in the growing velvet antler of the red deer Cervus elaphus. Department of Physiology and Centre for Gene Research, Otago School of Medical Sciences, Dunedin, New Zealand.

Antlers are organs of bone which regenerate each year from the heads of male deer. In addition to bone, support tissues such as nerves also regenerate. Nerves must grow at up to 1 cm/day. The control of this rapid growth of nerves is unknown We examined the relative expression of neurotrophin-3 (NT-3) mRNA in the different tissues of the growing antler tip and along the epidermal/dermal layer of the antler shaft of the red deer Cervus elaphus, using semi-quantitative reverse transcription chain reaction. Expression in the tip was found to be highest in the epidermal/dermal layer and lowest in the cartilaginous layer in all developmental stages examined. These data correlate well with the density and pattern of innervation of these tissues. Along the epidermal/dermal layer of the antler shaft, expression was highest in the segments subjacent to the tip and lowest near the base, arguing for differences in the temporal expression of NT in these segments. The expression of NT-3 in cells isolated from the different layers of 60 day antlers did not mirror that observed when whole tissues were used and may suggest regional specificity of NT-3 expression within antler tissues.

Goss, R. J. 1983. Deer antlers. Regeneration, Function, and evolution. Academic Press Inc., Orlando FL (ISBN 0-12-293080-0), 336p.

Goss RJ Anat Rec 1995 Mar;241 (3):291 -302 Future directions in antler research. Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912, USA.

Through a series of interrogatories, unsolved problems of antler evolution, anatomy, development, physiology, and pathology are probed, with commentaries, on the following prospects for future research:

1. How could these improbable appendages have evolved mechanisms to commit suicide, jettison the corpse, and regenerate new ones every year?
2. By what developmental processes are antlers able to prescribe their own morphogenesis with mirror image accuracy year after year and in some cases produce deliberate asymmetries?
3. What causes the scalp to transform into velvet skin as a deer's first antlers develop?
4. Why do healing pedicle stumps give rise to antler buds instead of scar tissue?
5. How is the unprecedented rate of antler elongation related to the diameter and length of the structure to be grown?
6. How come wound healing by pedicle skin is held in abeyance for several months until new growth resumes?
7. How is it that tropical deer regenerate antlers at any time of year, while in temperate zones deer do so in seasonal unison?
8. How do deer find enough calcium to make such massive antlers in only a few months?
9. What is the nature of the bizarre tumors that some antlers grow following castration?

Gray, C. M., Taylor, M.L., Horton, M.A., Loudon, A.S.I., and Arnett, T.R. 1989. Studies with cells derived from growing deer antler. J. Endocrinol. 123: 91.

Gray C, Hukkanen M, Konttinen YT, Terenghi G, Arnett TR, Jones SJ, Burnstock G, Polak JM Neuroscience 1992 Oct;50{4):953-963 Rapid neural growth: calcitonin gene-related peptide and substance P-containing nerves attain exceptional growth rates in regenerating deer antler. Department of Anatomy and Developmental Biology, University College, London, U.K.

Deer antler is a unique mineralized tissue which can produce very high growth rates of >1 cm/day in large species. On completion of antler growth, the dermal tissues which cover the antler are shed and the underlying calcified tissue dies. After several months the old antler is discarded and growth of a new one begins. It is known that deer antlers are sensitive to touch and are innervated. The major aims of this study were to identify and localize by immunohistochemical techniques the type of innervation present, and to find out whether nerve fibres could exhibit growth rates comparable to those of antler. We have taken tissue sections from the tip and shaft of growing Red deer (Cervus elaphus) antlers at three stages of development; shortly after the initiation of regrowth, the rapid growth phase, and near the end of growth. Incubation of tissue sections with antisera to protein gene product 9.5 (a neural cytoplasmic protein), neurofilament triplet proteins (a neural cytoskeletal protein), substance P and calcitonin gene-related peptide (both of which are present in and synthesized by sensory neurons) showed the presence of immunoreactive nerve fibres in dermal, deep connective and perichondrial/periosteal tissues at all stages of antler growth. The sparse distribution of vasoactive intestinal polypeptide-like immunoreactivity was found in dermal tissue only at the earliest stage of antler development. Nerve fibres inimunoreactive to neuropeptide Y, C-flanking peptide of neuropeptide Y and tyrosine hydroxylase, all present in postganglionic sympathetic nerves, were not observed at any stage of antler growth. Nerves expressing immunoreactivity for any of the neural markers or pepticles employed could not be found in cartilage, osteoid or bone. These results show that antlers are innervated mainly by sensory nerves and that nerves can attain the exceptionally high growth rates found in regenerating antler.

Ha, H., S. H. Yoon, et al 1990. Study for new hapatotropic agent from natural resources. I. Effect of antler and old antler on liver injury induced by benzopyrene in rats. Proc. Japanese Soc. Food & Nutrition 23: 9.

Han, S. H. 1970. Influence of antler (deer horn) on the enterochromaffin cells in the gastrointestinal mucosa of rats exposed to starvation, heat, cold and electric shock. J. Catholic Medical College 19: 157-164.

Hattori, M, X-W Yang, S. Kaneko, Y. Nomura & T. Namba. 1989. Constituents of the pilose antler of Cervus nippon. Shoyakugaku Zasshi 43: 173-176.

Huang SL, Kakiuchi N, Hattori M, Namba I Chem Pharm Bull (Tokyo) 1991 Feb;39(2):384-387A new monitoring system of cultured rnyocardial cell motion: effect of pilose antler extract and cardioactive agents on spontaneous beating of myocardial cell sheets. Research Institute for Wakan-yaku (Traditional Sino-Japanese Medicines), Toyama Medical and Pharmaceutical University.

Effects of various cardioactive agents and a water extract of the pilose antler of Cervus nippon var. mantchuricus on periodic beating of cultured myocardial cell sheets were examined by using an image analyzing system. Norepinephrine increased the beating rate and the beating amplitude, whereas digoxin and forskolin enlarged only the beating amplitude. Verapamil and propranolol decreased both the beating rate and the beating amplitude. The water extract of the pilose antler showed no remarkable effects in a standard medium (2.1 mM Ca2÷). However, it significantly increased the beating amplitude when the beating was suppressed by replacement with a low calcium medium (0.5 mM Ca2+). A similar effect was found for 70% ethanol-soluble and -insoluble fractions of the extract.

Ivankina NF, Isay SV, Busarova HG, Mischenko Tya Comp Biochem Physiol [ 1993 Sep;106(l):159- 162 Prostaglandin-like activity, fatty acid and phospholipid composition of sika deer (Cervus nippon) antlers at different growth stages. State Medical Institute, Blagoveschensk, Russia.

1. The alteration of lipid composition has been shown to take place at different stages of antler growth, 2. The greatest amounts of phospholipids and polyunsaturated fatty acids have been found during the most intense soft antler growth period. 3. The bioregulators of lipid origin which are prostaglandins of A, B, E and F groups have been found at the same stage.

Kang, W. 5. 1970. Influence of antler (deer horn) on the mesenteric mast cells of rates exposed to heat, cold or electric shock. J. Cathol. Med. College 19: 1-9.

Kaptchuk, T. and M. Croucher. 1957. The Healing Arts: Exploring the Medical Ways of the World. New York, Summit Books.

Kim, Y. E., 0. K. Lim, et c 1977. Biochemical studies on antler (Cervus nippon taiouanus) V: A study of glycolipids and phosholipids of antler velvet Layer and pantocrin. Korean Biochem. J. 10: 153-164.

Kim, K. W. and S. W. Park. 1982. A study of the hemopoietic action of deer horn extract. Korean Biochem. J. 15: 151-157.

Kim, Y. E. and K. .5. Kim. 1983. Biochemical studies on antler (Cervus nippon taiouanus). VI. Comparative study on the effect of Lipid soluble fractions of antler sponge and velvet layers and pantocrin on the aldolase activity in the rat spinal nerves. Yakhak Hoeji 27: 235-243.

Kim, K. B. and S. I. Lee. 1985. Effects of several kinds of antler upon endocrine functions in rats. Kyung Hee Univ Med. J. ?8: 91-110.

Ko KM, Yip U, Tsao SW, Kong YC, Fennessy P, Belew MC, Porath J Gen Comp Endocrinol 1986 Sep;63(3):431 -440 Epidermal growth factor from deer (Cervus etaphus) submaxillary gland and velvet antler.

Epidermal growth factor (EGF)-like activity was isolated for the first time from the submaxillary gland (5MG) and the velvet antler of red deer (Cervus elaphus) by a combination of Sephadex gel or DEAE-Sephacel and IMAC columns in succession. The semipurified cervine EGF-like activity (cEGF), with specific activity of 4.7 ng/micrograms protein from the velvet tissues, can generate a completely parallel competitive binding curve against mouse EGF in both radioreceptor assay (RRA) and radioimmunoassay (RIA). Mitogenic activity of EGF from both tissues was demonstrated by stimulating the incorporation of [3H]thymidine in two different cell lines of fibroblast culture in a dose-dependent manner. The velvet layer may be the site of EGF synthesis outside the SMG.

Kong, Y., K. Ko, et al. 1987. Epidermal growth factor of the cervine velvet antler. Acta. Zool. Sin., 33: 301 -308:

Kaptchuck, T. and M. Creacher 1987. The healing arts: Exploring the medical ways of the world. Summit Books, New York, 176 pages.

Lewis LK, Barrell GK Steroids 1994 Aug; 59(8):490-492 Regional distribution of estradiol receptors in growing antlers. Animal and Veterinary Sciences Group, Lincoln University, Canterbury, New Zealand.

This study of estrogen receptors (ER) was carried out to confirm their presence and to determine their localisation in antler bones. Partially grown antlers were amputated from red deer (Cervus elaphus) stags, the skin removed, and samples taken of periosteum, cartilaginous tissue including perichondrium, and bone. Capacity and binding of free ER in the samples were calculated by Scatchard analysis of data obtained from a radioreceptor assay which utilised [3H]estradiol as tracer. High affinity ER (ka 1.3-3.4 x 10(10)/M) were detected in all tissues sampled with the exception of bone. Receptor capacity ranged from 12-74 fmol/mg protein, ranking the tissues for capacity in the following descending order: periosteum, cartilage, calcified cartilage. These results demonstrate the presence of ER in growing antlers and indicate regional localization of the receptors within these structures. The absence of ER in bone tissue within the antler suggests that the effect of estradiol on stimulation of mineralization in this tissue is indirect and must occur via its binding to the non-calcified tissues of antlers, e.g., periosteum, perichondrium, and cartilage.

Li C, Waldrup KA, Corson ID, Littlejohn RP, Suttie JM J Exp Zool 1995 Aug 1;272(5):345-355 Histogenesis of antlerogenic tissues cultivated in diffusion chambers in vivo in red deer (Cervus elaphus). AgResearch, Inverinay Agricultural Centre, Mosgiel, New Zealand.

In a previous study we showed that formation of deer pedicle and first antler proceeded through four ossification pattern change stages: intramembranous, transition, pedicle endochondral, and antler endochondral. In the present study antlerogenic tissues (antlerogenic periosteurn, apical periosteum/perichondrium, and apical perichondrial of pedicle and antler) taken from four developmental stages were cultivated in diffusion chambers in vivo as autografts for 42-68 days. The results showed that all the cultivated tissues without exception formed trabecular bone de novo, irrespective of whether they were forming osseous, osseocartilaginous, or cartilaginous tissue at the time of initial implant surgery; in two cases in the apical perichondria from antler group, avascularized cartilage also formed. Therefore, the antlerogenic cells, like the progenitor cells of somatic secondary type cartilage, have a tendency to differentiate into osteoblasts and then form trabecular bone. Consequently, the differentiation pathway whereby antlerogenic cells change from forming osteoblasts to forming chondroblasts during pedicle formation is caused by extrinsic factors. Both oxygen tension and mechanical pressure are postulated to be the factors that cause this alteration of the differentiation pathway.

Marchenko LI, Kats MA Vrach Delo 1975 Aug;8:135-136 Anaphylactic shock as a response to subcutaneous administration of pantocrine. Article in Russian.

Miller SC, Bowman BM, Jee WS Bone 1995 Oct;17(4 Suppl):117S-1235 Available animal models of osteopenia- and large. Division of Radiobiology, School of Medicine, University of Utah, Salt Lake City 84112, USA

Animal models of osteopenia are reviewed. Endocrine excess or deficiency conditions include ovariectomy, orchidectomy, glucocorticoid excess and other endocrine states. Seasonal and reproductive cycles are usually transient and include pregnancy and lactation, egg-laying, antler formation and hibernation. Dietary conditions include calcium deficiencies, phosphate excess and vitamin C and D deficiencies. Mechanical usage effects include skeletal underloading models. Aging is also associated with osteopenia in many species.

Muir, P. D., Sykes, A.It, Barrell, GK. 1988. Changes in blood content and histology during growth of antlers in red deer, Cervus elaphus, and their relationship to plasma testosterone levels. J. Anat. 1 58: 31-42.:

Narimanov AA, Kuznetsova SM, Miakisheva SN Radiobiologiia 1990 Mar;30(2):170-174 The modifying action of the Japanese pagoda tree (Sophora japonica) and pantocrine in radiation lesions. [Article in Russian]

A study was made of the effect of Sophora japonica and pantocrine on irradiated (2.5 Gy) human lymphoblastoid cells. The radioprotective effect was manifested with the preparations injected separately after irradiation. The highest radioprotective effect was produced by the mixture of the preparations, the injection 15 mm after irradiation being more effective than preinjection. The protective effect of the agents was studied on mongrel mice after the administration thereof for the purposes of protection protection-and-treatment and treatment. Sophora japonica and pantocrine were shown to increase the survival rate of lethally exposed mice (L090/30) when administered in a combination 5-15 mm before irradiation and when used for the purposes of protection--and--treatment: 53.3% and 50% of animals, respectively, survived by day 30 following irradiation. DMF was 1.25.

Price JS, Oyajobi 60, Nalin AM, Frazer .4, Russell RG, Sandell U 0ev Dyn 1996 Mar;205(3):332-347 Chondrogenesis in the regenerating antler tip in red deer: expression of collagen types I, IIA, IIB, and X demonstrated by in situ nucleic acid hybridization and immunocytochemistry. Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, U.K.

The annual regrowth of antlers in mate deer is a unique example of complete bone regeneration occurring in an adult animal. Growth is initiated at the distal antler tip, which is similar to the epiphyseal growth plate in some respects. However, there is some debate as to whether this process represents 'true' endochondral ossification. As part of the characterization of the developmental process in pre-osseous antler tissue, we have studied, by in situ hybridization, the spatial expression of mRNAs for types I, II, and X collagen. Viewed in a coronal plane, type I procollagen mRNA was observed in skin, the fibrous perichondrium, and the densely cellular area immediately adjacent to the perichondriurn. Below this area, as cells began to assume a columnar arrangement and coincident with the appearance of a vasculature and synthesis of a cartilaginous matrix, transcripts for types I, IIA, IIB procollagen and X collagen were detected. Further down in the cartilage zone, the pattern of type I procollagen mRNA expression was altered. Here, the signal was detected only in a morphologicafly distinct subpopulation of small, flattened cells within the intercellular matrix at the periphery of the columns of chondrocytes. The alternative splice form of type II procollagen mRNA (IIA), characteristic of chondroprogenitor cells (Sandell et al. [1991] J. Cell Biol. 114:1307-1319), was expressed by a subset of cells in the upper region of the columns, indicating that this zone contains a population of prechondrocytic cells. Positive hybridization to type IIA was most abundant in these cells. In contrast, transcripts for the other procollagen splice form (IIB) and type X collagen were expressed by chondrocytes throughout the whole of the cartilage region studied. The translation and export of type II collagen and type X collagen were confirmed by detecting specific immunoreactivity for each. The spatial distribution of immunoreactivity for collagen types II and X was consistent with that of corresponding mRNAs. These data demonstrate for the first time the distinct pattern of expression of genes for major cartilage matrix macromolecules, the expression of the differentially spliced form of type II procollagen mRNA (IIA) and specifically the co-localization of types II and X collagen in the developing antler tip. Taken together, they strongly indicate that antler growth involves an endochondral process.

Ramirez V, Brown RD Comp Biochem Physiol A 1988;89(2):279-281 A technique for the in vitro incubation of deer antler tissue. Caesar Kleberg Wildlife Research Institute, Texas M University, Kingsvilte 78363.

1. A procedure for the in vitro incubation of velvet deer antler tissue was developed. Biopsy samples were collected in June with a trephine from 2 adult white-tailed deer and incubated in modified BGJb medium up to 48 hr. Calcium (Ca) and hydroxyproline (OH-proline) concentrations in the tissue were determined.

2. A significant increase (P less than 0.05) in Ca was exhibited at 4 and 8 hr of incubation, and, after replenishment of media, at 48 hr.

3. Hydroxyproline concentrations continued to rise throughout the duration of the incubation period and were significantly higher than controls (P less than 0.05) at 16, 24, and 48 hr.

4. Results suggest antler tissue can be incubated in vitro with the protocol described, although length of incubation may vary with parameter measured.

Rucklidge GJ, Milne 6, Sos KJ, Farquharson C, Robins SP Comp Biochem Physiol B Biochem Mol Biol 1997 Oct;118(2):303-308 Deer antler does not represent a typical endochondral growth system: immunoidentification of collagen type X but little collagen type II in growing antler tissue. Rowett Research Institute, Bucksburn, Aberdeen, U.K. gjr@rri.sari.ac.uk

The collagen isotypes present at early (6 week) and late (5 month) stages of growing deer antler were isolated and identified. Pepsin-digested collagens were separated by differential salt fractionation, SDS-PAGE and Western blotting and subsequently identified by immunostaining. Cyanogen bromide digestion of antler tissue was used to establish a collagen type-specific pattern of peptides, and these were also identified by immunoblotting. Collagen type I was found to be the major collagen in both early- and Late-stage antler. Collagen type II was present in the young antler in small amounts but was not confined to the soft 'cartilaginous tip of the antler. Collagen type XI was found in the pepsin digest of the young antler, but collagen type IX was not present at either stage of antler growth. Collagen type X was found in the young antler in all fractions studied. Microscopic study showed that the deer antler did not possess a discrete growth plate as found in endochondral bone growth. Unequivocal immunolocalization of the different collagen types in the antler were unsuccessful. These results show that, despite the presence in the antler of many cartilage collagens, growth does not occur through a simple endochondral process.

Sadighi M, Haines SR, Skottner A, Harris A_I, Suttie JM .1 Endocrinol 1994 Dec;143(3):461-469 AgResearch, Invermay Agricultural Centre, Mosgiel, New Zealand Effects of insulin-like growth factor-I (IGF-I) and IGF-II on the growth of antler cells in vitro.

The effects of insulin-like growth factors -I and -II (IGF-I and -II) on the growth of undifferentiated (fibroblast zone) cells from the growing tip of red deer velvet antlers and from cells 1.5cm distal to the growing tip (cartilage zone) were investigated in primary cell culture. The addition of IGF-I or IGF-II to the medium of cultures preincubated in serum-free medium for 24 h increased the rate of [3H]thymidone uptake in a dose-dependent manner in both cell types, with maximal stimulation occurring when 1 nM-30 nM was added. The addition of GF-II to the incubation medium containing ICE-I did not cause a further increase in [ uptake in either cell type over and above each growth factor alone, indicating that there were unlikely to be synergistic effects of IGF-II on the mitogenicity of CF-I. Binding studies were carried out using 3 x 10(5) fibroblast zone cells and cartilage zone cells after they had been incubated in serum-free medium for 24 h. 125I-Labelled IGF-I (10(-9) M) in a final volume of 200 microliters was added to each culture and incubation carried out at 4 degrees C for a further hour. 125I-Labelled IGF-I bound specifically to both fibroblasts and cartilage zone cells; binding was displaced by both unlabelled IGF-I and by IGF-I antibody.

Sempere A_I, Grimberg R, Silve C, Tau C, Garabedian M Endocrinology 1989 Nov;125(5):2312-2319 Evidence for extrarenal production of 1,25-dihydroxyvitamin during physiological bone growth: in vivo and in vitro production by deer antler cells. Centre dttudes Biologiques des Animaux Sauvages (CNRS), Beauvoir-sur-Niort, France.

The development of deer antler follows a pattern similar to that described for mammalian endochondral ossification and has been proposed as a suitable model for studies of bone growth. We investigated seasonal changes in the plasma concentrations of 1 ,25-dihydroxyvitamin D [1,25-(OH)2D] and calcium and the activity of alkaline phosphatase in relation to the antler cycle during 1 yr in 4 captive roe deer and measured these biological parameters in 27 wild roe deer during their antler cycle. A significant elevation of 1,25-(OH)2D in peripheral plasma, with no parallel increase in the concentration of its precursor 25-hydroxyvitamin D, was observed to accompany the rapid growth phase of the antler cycle in captive (P less than 0.001) and wild (P less than 0.025) deer. During the same phase there was a gradient in levels of 1,25-(OH)2D in antler vs. jugular blood (P less than 0.01). In addition, velvet cells in culture proved to have the ability to convert 25-hydroxyvitamin D3 into a more polar derivative, which was indistinguishable from true 1,25-(OH)2D3 with regard to its chromatographic properties, its UV absorbance at 254 nm, and its ability to bind to the l,25-(OH)2D3 receptors present in chick intestinal cytosol. These in vivo and in vitro results strongly suggest that local production of l,25.(QH)2D by the antler cells does occur in vivo and may contribute to the increase in plasma 1,25-(OH)2D during bone growth.

Suttie, J. M., P.D. Gluckman, et al. 1985. Insulin like growth factor 1: antler stimulating hormone? Endocrinol. 116: 846-848:

Suttie, J. M., P. F Fennessy, et al 1989. Pulsatite growth hormone, insulin-like growth factors and antler development in red deer (Cervus elaphus scoticus) stags. J. Endocrinol. 121: 351 -360.

Suttie, J. M., P. F. Fennessy, et al. 1991. Antler growth in deer. Proc. Deer Course for Veterinarians (Deer Branch, N Vet Assoc) 8: 155-168.

Suttie, J. M., I. D. Corson, et al. 1991. Insulin-like growth factor 1, growth and body composition in red deer stags. Anim. Prod. 53: 237-242.

Sutti, J. M., Fennessy, P. F., Names, S. R., Sadighi, M., Kerr, D.R. and Issacs, C. 1994. The New Zealand velvet antler industry: Background and research findings. International symposium on Cervi Parvum Cornu. KSP Proceedings. Oct. , 1994. Seoul, Korea, pp 86-135.

Sim, J. S. Sunwoo, H. H. and Hudson, R. J. 1995a. Cell growth promoting factors in water-soluble fraction of Canadian elk (Cervus elaphus) antler. page 111, 1st International Conference on East-West Perspectives on Functional Foods, Singapore, September, 26-29, 1995.

Sim, J. S., Sunwoo, H. H., Hudson R. I and Kurylo, S. L. 1995b. Chemical and pharmacological characterization of Canadian elk (Cervus elaphus) antler extracts. page 68, 3rd World congress of medicinal acupuncture and natural medicine, Edmonton, Alberta, Canada, August 10-12-1995.

Sunwoo, H. N. Nakano, 1. Hudson, R. J. and Sim, J. S. 1995. Chemical composition of antlers from wapiti (Cervus elaphus). J. Agric. Food Chem. 43: 2846-2849.

Sunwoo, H. H. 1998. Isolation and characterization of proteoglycans in growing antlers of wapiti (Cervus elaphus). Chapter 8 In Chemical characterization of growing antlers of Wapiti (Cervus elaphus). Ph. D. thesis, University of Alberta.

Sunwoo, H. H, Nakano, T. and Sim, J. S. 1997. Effect of water soluble extract from antlers of wapiti (Cervus elaphus) on the growth of fibroblasts. Can. J. Anim. Sci. 77:343-345.

Sunwoo, H. H. and Sim, J. S. 1996. Chemical and pharmacological characterization of Canadian elk (Cervus elaphus) antler extracts. 96-World

Federation Symposium of Korean Scientists and Engineers Association, June 28 July 4, 1996, Seoul Korea, WFKSEA Prodeedings 96: 706-713.

Takikawa, K., N. Kokubu, et al. 1972. Studies on experimental whiplash injury. II. Evaluation of Pantui extracts, Pantocrin as a remedy. Folia Pharmacol. Japon. 68: 473-488. [Article in Japanese]

Takikawa, K., N. Kokubu, et al 1972. Studies on experimental whiplash injury. III. Changes in enzyme activiation of cervicxal cords and effect of Pantui extracts, Pantocrin as a remedy. Folia Pharmacol Japon. 68: 489-493.

Wang, B. X., X. H. Zhao, et al. 1988. Effects of repeated administration of deer antler extract on biochemical changes related to aging in senescence-accelerated mice. Chem. Pharm. Bull. 36: 2593-2 598.

Wang, B. X., X. H. Zhao, et al. 1988. Stimulating effect of deer antler extract on protein synthesis in senescence-accelerated mice in vivo. Chem. Pharm. Bull. 36: 2593-2598.

Wang, B. x, X. I-I. Zhao, et al. 1988. Inhibition of liquid peroxidation by deer antler (Rokujo) extract in vivo and in vitro. J. Med. Pharm. Soc. for WAKAN-Yaku 5: 123-128.

Wang BX, Zhao XH, Qi SB, Yang XW, Kaneko 5, Hattori M, Namba T, Nomura Y Chem Pharm Bull (Tokyo) 1988 Jul;36(7):2593-2593 Stimulating effect of deer antler extract on protein synthesis in senescence-accelerated mice in vivo.

Wang BX, Zhau QL Yao Hsueh Hsueh Pao 1991;26(9):714-720 Advances in the chemical, pharmacological and clinical studies on pilose antler. [Article in Chinese]

Wang BX, Liu AJ, Cheng Xi, Wang QG, Wei CR, Cui JC Yao Hsueh Hsueh Pao 1985 May;20(5):32I- 325 Anti-ulcer action of the polysaccharides isolated from pilose antler. [Article in Chinese]

Wang BX, Chen XG, Xu HB, Zhang W, Zhang J Yao Hsueh Hsueh Pao 1990;25(9):652-657 Effect of polyamines isolated from pilose antler (PASPA) on RNA polymerase activities in mouse liver. [Article in Chinese] Department of Pharmacology, Academy of Traditional Chinese Medicine, Changchun.

The incorporations of [3H] leucine into protein and [3H] uridine into RNA in mouse liver were increased when PASPA was given to mice at a dose of 30 mg/kg for 4 successive days. The RNA potymerase activity, especially the RNA polymerase II activity in the solubilized liver nuclear fraction of PASPA-treated mice was also increased. In vitro experiment demonstrated that PASPA increased the RNA polymerase activity significantly in mouse liver nuclei at a concentration of 1 microgram/ml. These results suggest that the enhancement of RNA polymerase activities, particularly RNA polymerase II activity, induced by PASPA treatment is responsible for the increase in synthesis of protein and RNA in mouse liver tissue.

Wang BX, Chen XC, Zhang W Yao Ilsueh Hsueh Pao 1990;25(5):321 -325 Influence of the active compounds isolated from pilose antler on syntheses of protein and RNA in mouse liver. [Article in Chinese] Department of Pharmacology, Academy of Traditional Chinese Medicine and Materia Medica of Jilin Province, Changchun.

The polyamines of pilose antler (PASPA) consist of putrescine (PU, 70.9%), spermidine (SPD, 26.3%) and spermine (SP, 2.8%). The incorporations of [3H] leucine into protein and [3H] uridine into RNA in mouse liver tissue were increased when PASPA was given orally to mice at the dose of 30 mg/kg for 4 successive days. The incorporations of [3H] leucine into liver protein and [3H] uridine into the cytosolic and nuclear RNA were also increased by treatment with PU (21 mg/kg). In addition, the RNA polymerase activity in the solubilized liver nuclear fraction of PU (21 mg/kg)-treated mice was increased. SPD only promoted the synthesis of protein in mouse liver tissue at the dose of 8 mg/kg. However, SP showed no effect on the synthesis of protein and RNA polymerase activity under the used dose (1 mg/kg). The results suggest that PASPA is the main active substance responsible for the promotion of the synthesis of protein and RNA in mouse liver.

Yoon P. 1989. The effect of deer horn on the experimental anemia of rabbits. Journal Pharmaochemical Society Korea. 8: 6-11.

Yudin, A. M. and Y L. Dubryakov 1974. A guide for the preparation and storage of uncalcified male antlers as a medicinal raw material. In Reindeer antlers, Academy of Sciences of the USSR. Far East Science Center. Vladivostok.

Zhao QC, Kiyohara H, Nagai T, Yamada H Carbohydr Res 1992 Jun 16;230(2):361 -372 Structure of the complement-activating proteoglycan from the pilose antler of Cervus nippon Temminck. Oriental Medicine Research Center, Kitasato Institute, Tokyo, Japan.

An anti-complementary polysaccharide, DWA-2, isolated from an unossified pilose antler of C. nippon Temminck by digestion with pronase, gel filtration, and affinity chromatography, consisted mainly of GalNAc, GlcA, IdpA,and sulfate in the molar ratios 1.0:0.6:0.3:0.8, and small proportions of Man, Gal, GlcNAc, and protein (4.5%). Methylation analysis, NMR spectroscopy, and degradation with enzymes indicated that DWA-2 contained chondroitin sulfate A-, B-, and C-Like moieties. DWA-2 showed potent anti-complementary activity, and crossed immunoelectrophoresis indicated that it cleaved complement C3 in the absence of Ca2+ ion. Digestion of DWA-2 with chondroitinase ABC or ACl reduced the anti-complementary activity to a low level, but digestion with chondroitinase B reduced the activity by approximately 40% and the enzyme-resistant fraction still showed a significant activity.

Zhao D, Zhang X, Zhou F, Wei Z, Tian H Chung Kuo Chung Yao Tsa Chih 1990 Jan;15(l):37-39 Relation of Fourier transform infrared spectroscopic characteristics of pilose antler and its traditional quality grade. [ in Chinese] Beijing Institute for Drug Control.

The relationship between ETIR characteristics of Pilose Antler and its traditional quality grade was studied and a rule governing its quality value "Z" was found. We have thus advanced a new objective target for preparing Pilose Antler tablets and powder.

Zhang ZQ Zhang Y, Wang BX, Zhou HO, Wang Y, Zhang H Yao Hsueh Hsueh Pao 1992;27(5):321 -324 Purification and partial characterization of anti-inflammatory peptide from pilose antler of Cervus nippon Temminck. Department of Pharmacology, Academy of Traditional Chinese Medicine and Materia Medica of Jilin Province, Changchun.

An anti-inflammatory compound was purified and isolated from pilose antler of Cervus nippon Temminck by dialysis, gel filtration and ion-exchange chromatography techniques. HPLC and N- terminal amino acid analysis identified the compound as a homogeneous peptide. The peptide is composed of 68 amino acids and its molecular weight as determined by amino analysis, is about 7200.

Zhiliaev CV, Dobriakov lul K Med (Mosk) 1995;73(5):77-78 Experience in the use of rantarine in the treatment of internal diseases. [Article in Russian]

Zioupos P, Wang XT, Currey JO J Biomech 1996 Aug;29(8):989-1002 Experimental and theoretical quantification of the development of damage in fatigue tests of bone and antler. Department of Biology, University of York, U.K.

This study concerns the development of damage (as measured by a reduction in elastic modulus) in two kinds of bones differing considerably in their degrees of mineralisation: laminar bone from bovine femur and osteonal bone from red deer antler. Antler bone is much tougher than 'ordinary bone and its failure properties have been investigated in: (i) monotonic tensile tests and (ii) creep rupture experiments. Tensile fatigue is another way of examining how damage develops in bone. The development of damage in the present fatigue tests was non-linear with the cycle number, the degree of non-linearity was dependent on the level of stress and followed a clearly different course for bone and antler. Antler was a more damage-tolerant material, being able to achieve a reduction in the final modulus of elasticity, just prior to failure, three times greater than 'ordinary' bone. The evolution of damage is quantified by an empirical and a graphical method and by the use of Continuum Damage Mechanics (CDM) expressions. The CDM method shows important conditions, found in antler, but not in bone, that seen necessary for achieving stable fractures and consequently producing very tough materials.

Compiled for Elk Tech International